This invention relates to methods and apparatuses for identifying and alleviating deficiencies in the performance of semantic memory tasks, and particularly to the early diagnosis and treatment of Alzheimer's disease by identifying, as a symptom thereof, deficiencies in the performance of semantic memory tasks.
Studies of event-related potentials in subjects with dementia caused by Alzheimer's disease (Dementia of the Alzheimer Type, or "DAT") have demonstrated prolonged "P300" latencies in a majority of those subjects. An event-related potential ("ERP") is an electrical potential produced at the scalp of an individual representative of brain electrical activity resulting from the brain's response to external stimuli. It is picked up as a standard electroencephalograph ("EEG") signal and can be represented as a waveform of electrical potential as a function of time. The P300 component of that signal is the component with the most positive-going peak of the waveform in the latency range of 270 through 550 milliseconds. Latency means the time period following presentation of a stimulus until the subject event occurs. Ordinarily, an ERP exhibits a P300 component in response to perception by the subject of an unexpected or low-probability stimulus.
However, in the aforementioned studies, subjects from several etiologic groups were combined, and their pattern of cognitive deficits was not detailed. Thus, P300 prolongation could have been due to non-specific deficits in perceptual processing or attention capacity. Moreover, those studies used a simple auditory tone discrimination task, which was found not to be very sensitive in cases of mild dementia.
The diagnosis of Alzheimer's disease is most difficult in its early stages when only mild dementia is likely to be caused. This is because distinguishing the pathological memory loss caused by Alzheimer's disease from the far more common benign senescent forgetfulness has heretofore not been possible until the memory disorder is quite advanced, by which time the effects of associated cognitive impairments on mental status testing, coupled with a thorough evaluation, can bring the diagnostic accuracy to around 90 percent.
Early diagnosis of Alzheimer's disease is an important goal, as it can lead to better understanding of, and possible remedial strategies for, mild cognitive impairment, and can also permit more prompt treatment. A more powerful ERP technique than the classic auditory tone paradigm would therefore be helpful as a diagnostic and treatment tool.
It has previously been shown that, in young intact subjects, tasks that require processing of word meanings (semantic processing) enhance the amplitude of the P300 response associated with processing of the word meanings (as well as later memory for the word meanings) relative to tasks that only require phonologic or orthographic processing of the word. A semantic memory task will be defined herein as a task which involves the attempt to identify a stimulus as having a meaning to the subject. It would be desirable if the response to such tasks could be employed to diagnose early dementia of the type associated with Alzheimer's disease.
Electroencephalograph signals have previously been employed to ascertain the functional characteristics of a subject. For example, in John U.S. Pat. No. 4,216,781, analysis of a subject's brain wave responses to stimuli is used to determine, inter alia, the subject's ability to distinguish between symbols. Bergelson, et al. U.S. Pat. No. 4,493,327 discloses ascertaining the presence or absence of brainstem evoked potentials in response to a stimulus. Rickards, U.S. Pat. No. 4,462,411 discloses measuring evoked potentials in response to an audio stimulus to determine the subject's hearing ability. And, Silva, et al. U.S. Pat. No. 4,008,712 and Agoston U.S. Pat. No. 4,184,485 appear to disclose systems for producing an audio indication of a person's brain wave frequency for measurement and biofeedback purposes. However, none discloses the measurement of P300 amplitude as a means for identifying semantic memory task deficiencies, or treating them.